The intrauterine environment affects the development of the growing embryo and an unsuitable environment can lead to termination of pregnancy. However, emerging research has shown that more subtle factors can potentially influence long-term health in the offspring. For instance, malnourished pregnant mothers produce smaller offspring that have a higher incidence of obesity, diabetes, and heart disease during adulthood. To this point, most published studies have focused on negative changes in offspring caused by detrimental diets or stressful behavior. However, in the Western world, maternal obesity is an ever-increasing problem and epidemiology studies are now pointing to metabolic derangements in their offspring. In an attempt to be pro-active, maternal voluntary exercise during pregnancy was chosen as a potential short-term intervention to improve health outcomes in offspring. Fasting circulating glucose and insulin levels were lower in offspring born to exercised dams compared to those born to non-exercised dams, and glucose disposal and insulin sensitivity were significantly improved. As a result, our hypothesis for this proposal is that maternal voluntary exercise during pregnancy and nursing will improve glucose regulation and decrease obesity and hypertension in offspring. The first aim is designed to determine whether maternal voluntary exercise can improve insulin sensitivity in offspring fed a normal, standard diet and protect against obesity, insulin resistance, and hypertension progression in high calorie diet-fed offspring. The second aim hopes to elucidate the mechanism for long-lasting insulin sensitivity in offspring born to exercised dams which is likely through enhanced insulin signaling. The third aim will determine whether maternal exercise can be used as an intervention to improve pathology outcomes in offspring resulting from maternal consumption of a high calorie diet or gestational diabetes mellitus. To explore these aims, female mice will be placed into sedentary or voluntary exercise groups. The exercise dams will have 24 hour access to running wheels before mating and throughout pregnancy and nursing. The maturing offspring will not have access to running wheels for any portion of the study. Obesity, glucose and insulin tolerance, and hypertension will be monitored in the offspring fed either standard or high calorie diet. These studies will provide important information on the potential positive impact maternal exercise can have on offspring health. Obesity, diabetes, and cardiovascular disease are at epidemic levels and interventions targeting gestation might be an efficient way to stem the tide. PUBLIC HEALTH RELEVANCE: Exercise is currently used as a treatment for gestational diabetes but the long-term influence of this intervention on offspring health has been ignored. The proposed studies will provide novel information on whether maternal exercise can be used as an intervention to decrease obesity, diabetes, and hypertension development in offspring. Maternal exercise during pregnancy is a very realistic intervention that may provide a lifetime of benefits for the next generation.